ArticleThe Journal of biological chemistry2015
The Natural Product N-Palmitoyl-l-leucine Selectively Inhibits Late Assembly of Human Spliceosomes.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- Molecular basis for the activation of human spliceosome.Nature communications · 2024Article
- Targeting splicing factors for cancer therapy.RNA (New York, N.Y.) · 2023Article
- Interrelationship between miRNA and splicing factors in pancreatic ductal adenocarcinoma.Epigenetics · 2022Review
- Impacts and mechanisms of alternative mRNA splicing in cancer metabolism, immune response, and therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Biology of the mRNA Splicing Machinery and Its Dysregulation in Cancer Providing Therapeutic Opportunities.International journal of molecular sciences · 2021Review
- Prostate cancer racial, socioeconomic, geographic disparities: targeting the genomic landscape and splicing events in search for diagnostic, prognostic and therapeutic targets.American journal of cancer research · 2021Review
- Molecular Network and Culture Media Variation Reveal a Complex Metabolic Profile inInternational journal of molecular sciences · 2020Article
- Roles and mechanisms of alternative splicing in cancer - implications for care.Nature reviews. Clinical oncology · 2020Review
- Targeting mRNA processing as an anticancer strategy.Nature reviews. Drug discovery · 2020Review
- Therapeutic approaches to treat human spliceosomal diseases.Current opinion in biotechnology · 2019Review
- Role of Alternative Splicing in Prostate Cancer Aggressiveness and Drug Resistance in African Americans.Advances in experimental medicine and biology · 2019Review
- Article
- A Challenging Pie to Splice: Drugging the Spliceosome.Angewandte Chemie (International ed. in English) · 2017Review
- Article
- Modulating splicing with small molecular inhibitors of the spliceosome.Wiley interdisciplinary reviews. RNA · 2017Review
- Article
- Therapeutic targeting of splicing in cancer.Nature medicine · 2016Review
- ATPγS stalls splicing after B complex formation but prior to spliceosome activation.RNA (New York, N.Y.) · 2016Article
- Small Molecule Modulators of Pre-mRNA Splicing in Cancer Therapy.Trends in molecular medicine · 2016Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The spliceosome is a dynamic complex of five structural RNAs and dozens of proteins, which assemble together to remove introns from nascent eukaryotic gene transcripts in a process called splicing. Small molecules that target different components of the spliceosome represent valuable research tools to investigate this complicated macromolecular machine. However, the current collection of spliceosome inhibitors is very limited. To expand the toolkit we used a high-throughput in vitro splicing assay to screen a collection of pre-fractions of natural compounds derived from marine bacteria for splicing inhibition. Further fractionation of initial hits generated individual peaks of splicing inhibitors that interfere with different stages of spliceosome assembly. With additional characterization of individual peaks, we identified N-palmitoyl-l-leucine as a new splicing inhibitor that blocks a late stage of spliceosome assembly. Structure-activity relationship analysis of the compound revealed that length of carbon chain is important for activity in splicing, as well as for effects on the cytological profile of cells in culture. Together these results demonstrate that our combination of in vitro splicing analysis with complex natural product libraries is a powerful strategy for identifying new small molecule tools with which to probe different aspects of spliceosome assembly and function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.